Navigation

Search

research

Previous and current research

I focus on two coherent issues: the precise characterization of progenitor populations to find out which in vitro conditions need to be provided to keep the balance between proliferation and differentiation potential. I also want to prove true differentiation of dopaminergic neurons in vitro. The knowledge gained about stem cells this way would help establish cell sources for transplantation strategies.

I investigate the effects of Lrrk2 expression and mutation on proliferation, differentiation and survival of mouse predopaminergic NSCs. These data will allow us to dissect the actions of Lrrk2 during the development of the dopaminergic system.

The aim of our work is to elucidate whether the differences between midbrain-derived NSCs and NSCs from the SVZ or DG are due to cell intrinsic mechanisms or whether cell extrinsic signals from the surrounding brain tissue suppress in vivo neurogenesis in the midbrain. Furthermore our efforts focus on manipulation of the stem cell niche within the midbrain aiming on the activation of these dormant NSCs as a cell source for endogenous cell replacement strategies, e.g. in Parkonson’s disease (Hermann 2008).

The aim of our work is the exact characterization of these OPCs-NSCs from the human brain in vivo and in vitro. A special focus is drawn on transcription factors involved in neuronal differentiation (e.g. SOX2, OLIG2). Furthermore we are working on approaches for manipulation of these human NSCs to become dopamine neurons. Thereby these human NSCs might be a potential cell source for autologous cell replacement therapies for example in Parkinson’s disease.

In the current project, we are focusing on examining the neuronal differentiation potential of these cells, whose investigation is a major precondition for their future use in neurodegenerative diseases, such as Parkinson’s disease.

We are examining adult hippocampal neurogenesis in Pitx3-mutant-mice, which phenotypically show an selective degeneration of DA neurons of the SN, while the ventral tegmental area (VTA) is unaffected in young animals and partial degenerates during adulthood. This genetic PD-animal-model gives us the opportunity to differentially investigate the influence of the SN and VTA on adult neurogenesis.

The aim of our project is to investigate the role of Notch1, VEGF and other hypoxia-inducible factors in adult hippocampal neurogenesis. We are using voluntary exercise (wheel running) as a well-established physiological stimulator of adult neurogenesis to investigate the expression of hypoxia related genes and growth-factors in vivo. Furthermore, we take advantage of two knock-out models that lack the expression of VEGF-receptor type 2 (flk1) and Hif-1a respectively in neural progenitor cells.

Identification of molecular targets to regulate mesencephalic neural stem cells behaviour in vitro and in vivo. Thus, we currently identify intracellular signaling pathways during dopaminergic specification of mesencephalic stem cells. Furthermore, within a CRTD project we try to establish a new transplantation therapy for Parkinson’s disease (the so-called „bridging transplantation“) by combining orthotopic transplantation of dopaminergic cells into the substantia nigra and targeted axonal outgrowth of the transplanted cells to the target area, the striatum. This appraoch has the great advantage of potential reconstruction and synaptic integration of the nigro-striatal pathway into the host brain.